1. Field of the Invention
This invention relates to novel corticosteroids. More specifically it relates to pregn-4-enes which are substituted at the 4 position with fluoro or chloro and are optionally substituted at C-6 with fluoro or chloro. The compounds are topically active anti-inflammatory agents in mammals. The invention further relates to pharmaceutically active compositions comprising the compound of the invention in combination with at least one pharmaceutically acceptable excipient.
2. Prior Art
4-Chlorohydrocortisone and 4-fluorohydrocortisone are known compounds. However, no biological activity is shown for these compounds. See Ernst Jucher, Process in Drug Research, Vol. 5, p. 50, Birkhauser Verlag Basel and Stuttart, 1963. Other chemically related compounds are disclosed in U.S. Pat. No. 2,714,601 to Fonken et al.; U.S. Pat. No. 3,127,424 to Adams et al; and U.S. Pat. No. 3,129,219 to Goly as being useful as intermediates. U.S. Pat. No. 3,232,960 to Magerlein et al discloses certain 4-fluoro-4-pregnenes which may also have double bonds at C-1 and C-6 which are useful as anti-inflammatories.
U.S. Pat. No. 3,192,301 to Westerhof discloses a process for making certain steroids. At column 3 of the patent the broad formula indicates that the patent relates to compounds of the general formula ##STR1## wherein R.sup.5 and R.sup.6 may be, i.a., halogen. However, the patent does not disclose the preparation of any 4,6.alpha.-dihalo steroids.
U.S. Pat. No. 3,707,537 to Kierstead discloses certain 4-chloro-6-halo-pregna-4,6-dienes which require the presence of a 6-7 double bond. Another patent which discloses the possibility of certain 4,6-dihalo-pregna-4-enes is U.S. Pat. No. 3,489,748 to Benningen and Muller. These compounds differ from the compounds of this invention in that the Benningen et al compounds exhibit a 16.alpha.-alkylthio group and have no substitution at the 17.alpha. position. Furthermore, there are no di-substituted compounds disclosed, only 4-chloro-pregna-4,6,16-triene-3,20-dione and the corresponding 16.alpha.-ethylthiopregna-4,6-diene.
Other 3-keto-.DELTA..sup.4 steroids are also known which are 6,6-difluoro substituted. See, for example, U.S. Pat. No. 3,219,673; U.S. Pat. No. 3,767,684; U.S. Pat. No. 3,822,253; U.S. Pat. No. 3,681,338; U.S. Pat. No. 3,718,673; U.S. Pat. No. 3,546,215; and U.S. Pat. No. 3,629,242.
A heretofore unknown series of compounds has now been disclovered which show high topical anti-inflammatory activity.